Considerable evidence exists linking the renal parenchyma to the degradation of a variety of peptides, some of which have important hormonal activities. Since uremic individuals have elevated levels of many hormones, or respond inappropriately to both stimulatory and suppressive maneuvers, it has been proposed that the reduction in functioning kidney mass associated with renal failure accounts for these abnormalities. However the role of uremia per se in the pathogenesis of endocrine disorders has not been adequately evaluated. The proposed investigation will address itself to these questions and attempt to clarify the contribution of the kidney to the metabolism of glucagon, insulin, and prolactin. In addition, the role of the uremic state per se in the pathogenesis of the hormonal abnormalities associated with renal failure will be evaluated. Hormonal levels and metabolic clearance rates will be measured by radioimmunoassay in control rats and animals rendered uremic by either renal ablative maneuvers (nephrectomy or ureteral ligation) or by a urine autoinfusion technique. Comparison of the effect of ureteral ligation and nephrectomy on hormonal levels will provide information about the inactivation of these peptides by the renal parenchyma. Evaluation of the hormonal responses of uremic animals with intact kidneys will shed light on the role of uremia per se in causing abnormalities of hormonal metabolism in renal insufficiency. In addition, hormone degradation experiments will be performed utilizing an isolated perfused rat kidney preparation.